Study of immunoglobulins in various body fluids, especially in serum, urine and cerebrospinal fluid is important for understanding the pathomechanism of a variety of diseases and for diagnosing and monitoring diseases. Protein electrophoresis and immunofixation electrophoresis are key techniques to identifiy protein abnormalities and to detect abnormal immunoglobulins (paraproteins) in body fluids. The paraproteins are the products of clonal or oligoclonal proliferation of plasma cells and, as such, may represent full immunoglobulins, free heavy chains, and/or free light chains of immunoglobulins. Correct identification of paraproteins can be hampered, however, by the occurrence of pseudoparaproteins. Pseudoparaproteins are normally occurring proteins that mimic monoclonal-proteins in protein electrophoretic patterns. Over the past year, we have observed new cases of urine pseudoparaproteins that had not been described in the existing literature. Using a combination of various analytical techniques (e.g., electrophoresis in agarose and polyacrylamide gel, immunoelectrophoresis, and mass spectrometry), we are now in the process to fully identify these pseudoparaproteins. In a collaborative study, we investigated protein electrophoresis, immunoelectrophoresis and immunofixation electrophoresis as predictors for high-risk phenotype in familial Waldenstrm macroglobulinemia. Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal gammopathy conditions such as Waldenstrm macroglobulinemia. Immunofixation electrophoresis is currently the most common method for isotyping of monoclonal gammopathy because of its superior sensitivity relative to immunoelectrophoresis. Using these methods, possible monoclonal gammopathy was studied in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of Waldenstrm macroglobulinemia. We found that small monoclonal bands detected by immunofixation electrophoresis in a familial context may be biologically meaningful, both as phenotypic biomarkers and, possibly, as predictors of high risk for Waldenstrm macroglobulinemia. Polyclonal immunoglobulin M may also be a marker of genetic susceptibility in Waldenstrm macroglobulinemia families. Larger studies are needed to confirm these observations.